BACKGROUND: People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (≥ 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting.
OBJECTIVES: To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (≥ 18 years) with heart failure - either HFrEF or HFpEF.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS: We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes.
AUTHORS' CONCLUSIONS: This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.
BACKGROUND: In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage.
OBJECTIVES: To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke.
SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers, and performed forward reference/cited reference searching in August 2020.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke.
DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. They assessed risk of bias of each study using the Risk of Bias 1 (RoB1) tool and overall certainty of the evidence for each outcome using the GRADE approach.
MAIN RESULTS: We included 11 studies involving 42,226 participants. Three new trials have been added since the last update (743 participants). As per the previous version of this review, two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 96% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99; 7 RCTs, 42,034 participants; moderate-certainty evidence). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat for an additional beneficial outcome 79).
AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved.
BACKGROUND: Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016.
OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health-related quality of life (HRQoL) in people with CHD.
SEARCH METHODS: We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease.
DATA COLLECTION AND ANALYSIS: We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta-analysis by duration of follow-up: short-term (6 to 12 months); medium-term (> 12 to 36 months); and long-term ( > 3 years), and used meta-regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow-up time point). MAIN RESULTS: This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post-MI and post-revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty-one of the included trials were performed in low- and middle-income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow-up time was 12 months (range 6 months to 19 years). At short-term follow-up (6 to 12 months), exercise-based CR likely results in a slight reduction in all-cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all-cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials; NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise-based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow-up. We are uncertain about the effects of exercise-based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I2 = 53%), and of small study bias for all-cause hospitalisation, but not for all other outcomes. At medium-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all-cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise-based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta-regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow-up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise-based CR may slightly increase HRQoL across several subscales (SF-36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow-up; however, these may not be clinically important differences. The eight trial-based economic evaluation studies showed exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs).
AUTHORS' CONCLUSIONS: This updated Cochrane Review supports the conclusions of the previous version, that exercise-based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all-cause mortality, and a large reduction in all-cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow-up. Over longer-term follow-up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well-designed, adequately-reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer-term follow-up, and assess costs and cost-effectiveness.
Background: Stroke is the third leading cause of early death worldwide. Most ischaemic strokes are caused by a blood clot blocking an artery in the brain. Patient outcomes might be improved if they are offered anticoagulants that reduce their risk of developing new blood clots and do not increase the risk of bleeding. This is an update of a Cochrane Review first published in 1995, with updates in 2004, 2008, and 2015. Objectives: To assess the effectiveness and safety of early anticoagulation (within the first 14 days of onset) for people with acute presumed or confirmed ischaemic stroke. Our hypotheses were that, compared with a policy of avoiding their use, early anticoagulation would be associated with:. • reduced risk of death or dependence in activities of daily living a few months after stroke onset;. • reduced risk of early recurrent ischaemic stroke;. • increased risk of symptomatic intracranial and extracranial haemorrhage; and. • reduced risk of deep vein thrombosis and pulmonary embolism. Search methods: We searched the Cochrane Stroke Group Trials Register (August 2021); the Cochrane Database of Systematic Reviews (CDSR); the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 7), in the Cochrane Library (searched 5 August 2021); MEDLINE (2014 to 5 August 2021); and Embase (2014 to 5 August 2021). In addition, we searched ongoing trials registries and reference lists of relevant papers. For previous versions of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies. Selection criteria: Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in people with acute presumed or confirmed ischaemic stroke. Data collection and analysis: Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. We assessed the overall certainty of the evidence for each outcome using RoB1 and GRADE methods. Main results: We included 28 trials involving 24,025 participants. Quality of the trials varied considerably. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition, or reporting bias. Anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Over 90% of the evidence is related to effects of anticoagulant therapy initiated within the first 48 hours of onset. No evidence suggests that early anticoagulation reduced the odds of death or dependence at the end of follow-up (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 12 RCTs, 22,428 participants; high-certainty evidence). Similarly, we found no evidence suggesting that anticoagulant therapy started within the first 14 days of stroke onset reduced the odds of death from all causes (OR 0.99, 95% CI 0.90 to 1.09; 22 RCTs, 22,602 participants; low-certainty evidence) during the treatment period. Although early anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.75, 95% CI 0.65 to 0.88; 12 RCTs, 21,665 participants; moderate-certainty evidence), it was also associated with an increase in symptomatic intracranial haemorrhage (OR 2.47; 95% CI 1.90 to 3.21; 20 RCTs, 23,221 participants; moderate-certainty evidence). Similarly, early anticoagulation reduced the frequency of symptomatic pulmonary emboli (OR 0.60, 95% CI 0.44 to 0.81; 14 RCTs, 22,544 participants; high-certainty evidence), but this benefit was offset by an increase in extracranial haemorrhage (OR 2.99, 95% CI 2.24 to 3.99; 18 RCTs, 22,255 participants; moderate-certainty evidence). Authors' conclusions: Since the last version of this review, four new relevant studies have been published, and conclusions remain consistent. People who have early anticoagulant therapy after acute ischaemic stroke do not demonstrate any net short- or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis, and pulmonary embolism but increased bleeding risk. Data do not support the routine use of any of the currently available anticoagulants for acute ischaemic stroke.
BACKGROUND: Levels of physical activity and physical fitness are low after stroke. Interventions to increase physical fitness could reduce mortality and reduce disability through increased function.
OBJECTIVES: The primary objectives of this updated review were to determine whether fitness training after stroke reduces death, death or dependence, and disability. The secondary objectives were to determine the effects of training on adverse events, risk factors, physical fitness, mobility, physical function, health status and quality of life, mood, and cognitive function.
SEARCH METHODS: In July 2018 we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and four additional databases. We also searched ongoing trials registers and conference proceedings, screened reference lists, and contacted experts in the field.
SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses and assessed the quality of the evidence using the GRADE approach. Diverse outcome measures limited the intended analyses.
MAIN RESULTS: We included 75 studies, involving 3017 mostly ambulatory participants, which comprised cardiorespiratory (32 studies, 1631 participants), resistance (20 studies, 779 participants), and mixed training interventions (23 studies, 1207 participants). Death was not influenced by any intervention; risk differences were all 0.00 (low-certainty evidence). There were few deaths overall (19/3017 at end of intervention and 19/1469 at end of follow-up). None of the studies assessed death or dependence as a composite outcome. Disability scores were improved at end of intervention by cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% CI 0.19 to 0.84; 8 studies, 462 participants; P = 0.002; moderate-certainty evidence) and mixed training (SMD 0.23, 95% CI 0.03 to 0.42; 9 studies, 604 participants; P = 0.02; low-certainty evidence). There were too few data to assess the effects of resistance training on disability. Secondary outcomes showed multiple benefits for physical fitness (VO2 peak and strength), mobility (walking speed) and physical function (balance). These physical effects tended to be intervention-specific with the evidence mostly low or moderate certainty. Risk factor data were limited or showed no effects apart from cardiorespiratory fitness (VO2 peak), which increased after cardiorespiratory training (mean difference (MD) 3.40 mL/kg/min, 95% CI 2.98 to 3.83; 9 studies, 438 participants; moderate-certainty evidence). There was no evidence of any serious adverse events. Lack of data prevents conclusions about effects of training on mood, quality of life, and cognition. Lack of data also meant benefits at follow-up (i.e. after training had stopped) were unclear but some mobility benefits did persist. Risk of bias varied across studies but imbalanced amounts of exposure in control and intervention groups was a common issue affecting many comparisons.
AUTHORS' CONCLUSIONS: Few deaths overall suggest exercise is a safe intervention but means we cannot determine whether exercise reduces mortality or the chance of death or dependency. Cardiorespiratory training and, to a lesser extent mixed training, reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve fitness, balance and the speed and capacity of walking. The magnitude of VO2 peak increase after cardiorespiratory training has been suggested to reduce risk of stroke hospitalisation by ˜7%. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription, the range of benefits and any long-term benefits.
ANTECEDENTES: La mayoría de los accidentes cerebrovasculares se deben a la obstrucción de una arteria en el cerebro por un coágulo de sangre. El tratamiento inmediato con fármacos trombolíticos puede restaurar el flujo sanguíneo antes de que ocurra un daño mayor cerebro y mejorar la recuperación después del accidente cerebrovascular en algunas personas. Los fármacos trombolíticos, sin embargo, también pueden causar hemorragias graves en el cerebro, que puede ser fatal. Un medicamento, activador del plasminógeno tisular recombinante (rt-PA), está autorizado para su uso en pacientes seleccionados dentro de 4,5 horas de ictus en Europa y en el plazo de tres horas en el EE.UU.. Hay un límite máximo de edad de 80 años en algunos países, y una limitación para acariciar principalmente no grave en los otros. Están disponibles desde esta revisión fue actualizado en 2009 cuarenta por ciento más datos.
Determinar si, y en qué circunstancias, la terapia trombolítica podría ser un tratamiento eficaz y seguro para el accidente cerebrovascular isquémico agudo.
BUSCAR MÉTODOS: Se realizaron búsquedas en el Registro Cochrane de Ensayos Stroke Group (última búsqueda en noviembre de 2013), MEDLINE (1966 a noviembre de 2013) y EMBASE (1980 a noviembre de 2013). También manuales en las actas de congresos y revistas, listas de referencias y se estableció contacto con compañías farmacéuticas y autores de los ensayos.
Criterios de selección: Ensayos aleatorios de cualquier agente trombolítico comparado con controles en pacientes con accidente cerebrovascular isquémico definitivo.
Recopilación y análisis de datos Dos revisores aplicaron los criterios de inclusión, extrajeron los datos y evaluaron su calidad. Verificamos los datos extraídos con los investigadores de los principales ensayos, la obtención de datos no publicados adicionales si están disponibles.
Resultados principales: Se incluyeron 27 ensayos, con 10.187 participantes, poniendo a prueba la uroquinasa, estreptoquinasa, rt-PA, recombinante prouroquinasa o desmoteplase. Cuatro ensayos utilizaron administración intra-arterial, mientras que el resto utiliza la vía intravenosa. La mayoría de los datos provienen de ensayos que comenzaron el tratamiento hasta seis horas después del accidente cerebrovascular. Alrededor del 44% de los ensayos (alrededor del 70% de los participantes) fueron probando rt-PA intravenoso. En estudios anteriores muy pocos de los participantes (0,5%) fueron mayores de 80 años; En esta actualización, el 16% de los participantes son más de 80 años de edad, debido a la inclusión del IST-3 (53% de los participantes en este estudio tenían una edad de 80 años). Ensayos publicados más recientemente utilizados aleatorización computarizado, por lo que hay menos probabilidades de ser diferencias iniciales que en las versiones anteriores de la revisión. Más del 50% de los ensayos cumplió los criterios para la ocultación de alto grado; había pocas pérdidas durante el seguimiento de los principales resultados.
La terapia trombolítica, en su mayoría administrados hasta seis horas después del accidente cerebrovascular isquémico, redujo significativamente la proporción de participantes que estaban muertos o dependientes (Rankin modificada 3 a 6) en tres a seis meses de ictus (odds ratio (OR) 0,85; intervalo de confianza del 95% después (IC) 0,78 hasta 0,93). La terapia trombolítica aumenta el riesgo de hemorragia intracraneal sintomática (OR 3,75; IC del 95%: 3,11 a 4,51), la muerte temprana (OR 1,69; IC del 95%: 1,44 a 1,98; 13 ensayos, 7458 participantes) y la muerte de tres a seis meses después del accidente cerebrovascular ( OR 1.18, 95% CI 01.06 a 01.30). La muerte prematura después de la trombolisis fue principalmente atribuible a la hemorragia intracraneal. Tratamiento en las tres horas de carrera fue más eficaz en la reducción de la muerte o la dependencia (OR 0,66; IC del 95%: 0,56 a 0,79) sin ningún aumento en la muerte (OR 0,99; IC del 95%: 0,82 a 1,21; 11 ensayos, 2187 participantes). Hubo heterogeneidad entre los ensayos. Fármacos antitrombóticos contemporáneas aumentaron el riesgo de muerte. Pruebas de ensayos rt-PA mostró una reducción significativa de la muerte o la dependencia con el tratamiento hasta seis horas (OR 0.84, IC 95%: 0,77 a 0,93; p = 0,0006; 8 ensayos, 6729 participantes) con una heterogeneidad significativa; tratamiento dentro de tres horas fue más beneficiosa (OR 0.65, IC 95%: 0,54 a 0,80; p <0,0001; 6 ensayos, 1779 participantes) sin heterogeneidad. Los participantes mayores de 80 años se beneficiaron por igual a los menores de 80 años, sobre todo si se tratan dentro de tres horas del accidente cerebrovascular.
Conclusiones de los revisores: El tratamiento trombolítico dado hasta seis horas después del accidente cerebrovascular reduce la proporción de personas muertas o dependientes. Los tratados dentro de las primeras tres horas derivan sustancialmente más beneficios que con el tratamiento posterior. Este beneficio global fue evidente a pesar de un aumento de la hemorragia intracraneal sintomática, muertes en siete a 10 días, y las muertes en el seguimiento final (a excepción de las pruebas de ensayos rt-PA, que no tuvo ningún efecto sobre la muerte en el seguimiento final). Se necesitan ensayos adicionales para identificar la ventana de tiempo más reciente, si las personas con leve ventaja golpe desde la trombólisis, para encontrar formas de reducir la hemorragia intracraneal sintomática y muertes, y para identificar el entorno en el que la trombolisis mejor se puede dar en la práctica habitual.
OBJETIVO: Clarificar si algún β bloqueador específico es superior en los pacientes con insuficiencia cardíaca y fracción de eyección disminuída o si los beneficios de estos agentes se deben principalmente a un efecto de clase.
DISEÑO: Revisión sistemática y metanálisis en red de la eficacia de diferentes β bloqueadores en la insuficiencia cardíaca.
FUENTES DE INFORMACIÓN: CINAHL (1982-2011), Registro Cochrane Central de Ensayos Controlados (-2011), Embase (1980 a 2011), Medline / PubMed (1966-2011) y Web of Science (1965-2011).
ESTUDIO DE SELECCIÓN: Estudios aleatorizados que comparaban los β bloqueadores con otros β bloqueadores u otros tratamientos.
EXTRACCIÓN DE DATOS: El desenlace primario fue la mortalidad por todas las causas en el seguimiento más largo disponible, evaluado con Odds Ratios e intervalos creíbles con efecto aleatorizado Bayesiano al 95% con extracción independiente de datos por parte de los observadores.
RESULTADOS: Se incluyeron 21 estudios, centrándose en el atenolol, bisoprolol, bucindolol, carvedilol, metoprolol y nebivolol. Como se esperaba, en el análisis global, los β bloqueadores proporcionan beneficios creíbles en la mortalidad en comparación con el placebo o el tratamiento estándar después de una mediana de 12 meses (Odds Ratio 0,69, 0,56 a 0,80). Sin embargo, no se encontraron diferencias evidentes al comparar el riesgo de muerte, muerte súbita cardíaca, muerte por falla de bomba o interrupción del tratamiento entre los diferentes β bloqueadores uno por uno. De acuerdo con ello, las mejoras en la fracción de eyección del ventrículo izquierdo también fueron similares independientemente del fármaco en estudio.
CONCLUSIÓN: Los beneficios de los β bloqueadores en los pacientes con insuficiencia cardíaca con fracción de eyección reducida parece ser debido principalmente a un efecto de clase, ya que no hay evidencia estadística de los estudios actuales que apoye la superioridad de algún agente único en comparación con los otros.
ANTECEDENTES: La medida en que las estatinas individuales varían en función de los resultados clínicos a través de todas las poblaciones, además de la prevención primaria y secundaria no se ha estudiado ampliamente en los metanálisis.
MÉTODOS: Se estudiaron sistemáticamente 199.721 participantes en 92 estudios controlados con placebo y comparador activo que comparan la atorvastatina, fluvastatina, lovastatina, pravastatina, rosuvastatina y simvastatina en los participantes con o en riesgo de desarrollar enfermedad cardiovascular. Se realizó por pares y la red metanálisis para los principales eventos coronarios y los resultados de mortalidad por todas las causas, teniendo en cuenta las diferencias de dosis entre los ensayos. Registro Revisión sistemática: PROSPERO 2011: CRD42011001470.
RESULTADOS: Hubo pocos ensayos que evaluaron la fluvastatina. La mayoría de las comparaciones frecuentes ocurrieron entre pravastatina y placebo, atorvastatina y placebo, y rosuvastatina y atorvastatina. Ningún ensayo comparó directamente los seis estatinas entre sí. En todas las poblaciones, las estatinas fueron significativamente más eficaz que el control en la reducción de la mortalidad por todas las causas (OR 0,87, 95% intervalo de credibilidad 0,82-0,92) y los eventos coronarios mayores (OR 0,69; IC del 95%: 0,64 a 0,75). En términos de reducción de eventos coronarios mayores, atorvastatina (OR 0.66 IC 95% 0,48-0,94) y fluvastatina (OR 0.59, IC 95% 0,36-0,95) fueron significativamente más eficaz que la rosuvastatina en dosis comparables. En los participantes con enfermedad cardiovascular, las estatinas reducen significativamente las muertes (OR 0,82; IC del 95%: 0,75 a 0,90) y los eventos coronarios mayores (OR 0.69, IC 95% 0,62 hasta 0,77). Atorvastatina fue significativamente más eficaz que la pravastatina (OR 0,65; IC del 95%: 0,43 a 0,99) y simvastatina (OR 0,68; IC 95% 0,38-0,98) para la prevención secundaria de eventos coronarios mayores. En prevención primaria, las estatinas reducen significativamente las muertes (OR 0,91; IC del 95%: 0,83 hasta 0,99) y los eventos coronarios mayores (OR 0.69, IC 95%: 0,61 a 0,79), sin diferencias entre estatinas individuales. En todas las poblaciones, atorvastatina (80%), fluvastatina (79%), y simvastatina (62%) tuvieron la mayor probabilidad general de ser el mejor tratamiento en términos de resultados. Las dosis más altas de atorvastatina y fluvastatina tenían el mayor número de diferencias significativas en la prevención de eventos coronarios mayores en comparación con otras estatinas. No se detectó heterogeneidad o inconsistencia significativa.
CONCLUSIONES: Las estatinas reducen significativamente la incidencia de la mortalidad por todas las causas y los eventos coronarios mayores en comparación con el control, tanto en la prevención secundaria y primaria. Este análisis proporciona evidencia de diferencias de potencial entre las estatinas individuales, que no están plenamente explicados por sus efectos reductores del colesterol de lipoproteínas de baja densidad. Las diferencias observadas entre las estatinas deben investigarse en futuros estudios prospectivos.
ANTECEDENTES: La insuficiencia cardíaca crónica (IC) es un prevalente en todo el mundo. Bloqueadores de los receptores de angiotensina (ARA II) son ampliamente prescritos para la insuficiencia cardiaca crónica, aunque su papel es controvertido.
OBJETIVOS: Evaluar el beneficio y el daño de los ARA II en comparación con los inhibidores de la ECA (IECA) o placebo en la mortalidad, la morbilidad y abandonos por efectos adversos en pacientes con IC sintomática y disfunción sistólica del ventrículo izquierdo o de la función sistólica conservada.
MÉTODOS DE BÚSQUEDA: Los ensayos clínicos se identificaron mediante búsquedas en CENTRAL, HTA, y DARE, (The Cochrane Library 2010, número 3), así como en MEDLINE (2002 a julio de 2010) y EMBASE (2002 a julio de 2010). Las listas de referencias de artículos recuperados y las revisiones sistemáticas en busca de estudios adicionales no identificados por las búsquedas electrónicas.
CRITERIOS DE SELECCIÓN: doble ciego ensayos controlados aleatorios en los hombres y mujeres de todas las edades que tienen sintomática (NYHA clase II-IV) y HF: 1) la disfunción sistólica del ventrículo izquierdo, que se define como la fracción de eyección ventricular izquierda (FEVI) ≤ 40% o 2) la fracción de eyección conservada, definida como FEVI> 40%.
RECOPILACIÓN Y ANÁLISIS DE DATOS: Dos revisores evaluaron de forma independiente el riesgo de sesgo y extrajeron los datos de los estudios incluidos.
RESULTADOS PRINCIPALES: Veinte dos estudios evaluaron los efectos de los ARA II en 17.900 pacientes con FEVI ≤ 40% (promedio 2.2 años). ARA-II no redujo la mortalidad total (RR 0,87 [IC 95% 0,76, 1,00]) o la morbilidad total, medido por el total de hospitalizaciones (RR 0,94 [IC 95% 0,88, 1,01]) en comparación con el placebo.
La mortalidad total (RR 1,05 [IC 95% 0,91, 1,22]), el total de hospitalizaciones (RR 1,00 [IC 95% 0,92, 1,08]), IM (RR 1,00 [IC 95%: 0,62 a 1,63]), y el accidente cerebrovascular (RR 1,63 [ 0,77, 3,44]) no difirió entre los ARA II y los IECA, pero los retiros debidos a efectos adversos fueron menores con los ARA II (RR 0,63 [IC 95% 0,52, 0,76]). Las combinaciones de los ARA II más IECA aumenta el riesgo de retiros debidos a efectos adversos (RR 1,34 [IC 95%: 1,19 a 1,51]) pero no redujo la mortalidad total o los ingresos totales del hospital en comparación con IECA solo.
Dos estudios controlados con placebo evaluó los ARA II en 7151 pacientes con FEVI> 40% (media 3,7 años). ARA-II no redujo la mortalidad total (RR 1,02 [IC 95% 0,93, 1,12]) o la morbilidad total medido por el total de hospitalizaciones (RR 1,00 [IC 95% 0,97, 1,05]) en comparación con el placebo. Las retiradas por efectos adversos fueron mayores con los ARA II en comparación con el placebo cuando todos los pacientes fueron agrupados independientemente de la FEVI (RR 1,06 [IC 95% 1,01, 1,12]).
CONCLUSIONES DE LOS REVISORES: En los pacientes con IC sintomática y la disfunción sistólica o con fracción de eyección conservada, los ARA II frente a placebo o IECA no reducen la mortalidad total o la morbilidad. ARA se toleran mejor que IECA, pero no parece ser tan seguro y bien tolerado como el placebo en términos de los retiros debido a efectos adversos. Adición de un ARA-II en combinación con un IECA no reduce la mortalidad total o la hospitalización total, pero aumenta la retirada debido a efectos adversos en comparación con IECA solo.
Revista»European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology
ANTECEDENTES: La intolerancia a la glucosa (IGT) y la glucosa en ayunas (IFG) son estados prediabéticos, el tratamiento de los cuales pueden prevenir o retrasar la aparición de diabetes manifiesta y así reducir potencialmente importantes (CV) eventos cardiovasculares. Por lo tanto, tratamos de determinar si las intervenciones (incluyendo la dieta, el ejercicio y la terapia farmacológica), modificado por todas las causas y la mortalidad relacionada cardiovascular en estos temas.
MÉTODOS: Se realizó un meta-análisis de ensayos prospectivos, controlados aleatorios (ECA) que fueron identificados en la literatura médica y bases de datos. Los ensayos fueron elegibles para su inclusión si informaron todas las causas tasa de mortalidad (como mínimo), reclutado a unos 100 pacientes y tuvo un seguimiento mínimo de un año. Las intervenciones se dividieron en farmacológico y no farmacológico.
RESULTADOS: Diez ECA que incluyeron 23.152 pacientes cumplieron los criterios de entrada anteriores. Ensayos corrieron para un promedio de 3,75 años. La diabetes se ha retrasado o impedido por estas intervenciones versus control (riesgo relativo 0,83; IC del 95%: 0,80-0,86). Enfoques no farmacológicos (n = 3495) fueron superiores a los enfoques basados en drogas (n = 20.872) en la prevención de la diabetes (0,52, 0,46 a 0,58 vs 0,70, desde 0,58 hasta 0,85, P <0,05). No hubo diferencia en el riesgo de mortalidad por cualquier causa en la intervención del grupo control (0,96, 0,84 a 1,10) y no hubo diferencia en muerte CV (1,04, 0,61 a 1,78) frente. Hubo una tendencia no significativa hacia la reducción del infarto de miocardio mortal y no mortal (0,59, 0,23 a 1,50). Ictus mortal y no mortal estaba en el límite reducida (0,76, 0,58 hasta 0,99) con la intervención versus control.
CONCLUSIONES: A pesar de las intervenciones son en su mayoría éxito en el retraso de la progresión a diabetes manifiesta, esto no se tradujo en reducciones en todas las causas o la mortalidad cardiovascular o infarto de miocardio, con la posible excepción de un derrame cerebral.
People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (≥ 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting.
OBJECTIVES:
To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure.
SEARCH METHODS:
We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers.
SELECTION CRITERIA:
We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (≥ 18 years) with heart failure - either HFrEF or HFpEF.
DATA COLLECTION AND ANALYSIS:
We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS:
We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes.
AUTHORS' CONCLUSIONS:
This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.
